Huntington disease (HD) is a devastating neurodegenerative disorder with progressive deterioration of motor, cognitive and behavioral function caused by an unstable expansion of a CAG repeat. Although the disease producing defect has been known for more than a decade, there has been limited progress toward the successful development of pharmacological interventions which can prevent or delay the onset and progression of disease. There are a number of therapeutic agents that are being prepared for clinical trials; however, there are currently no sensitive and specific biomarkers of the earliest stages of disease progression that can be used to evaluate the efficacy of a neuroprotective agent. We have recently shown that certain types of saccades are a promising biomarker for prediagnostic and recently diagnosed HD (Blekher et al, 2004; Blekher et al, 2006). Based on our cross-sectional data, we hypothesize that the observed abnormalities in saccadic eye movements are actually progressive and correlated with increasing disease symptoms. In this exploratory application, we propose a series of cross sectional analyses to confirm our previous evidence for specific oculomotor biomarkers and to identify new nonredundant variables which can be employed, potentially in combination, as biomarkers of early HD progression. Through exploratory longitudinal analyses, we will also test whether individuals with an expanded number of CAG repeats have progressive worsening of their saccadic eye movements, olfactory identification and neurocognitive performance as they approach clinically-recognized, disease onset. In this exploratory application, we propose a series of cross sectional analyses to confirm our previous evidence for specific oculomotor biomarkers and to identify new nonredundant variables which can be employed, potentially in combination, as biomarkers of early HD progression. Through exploratory longitudinal analyses, we will also test whether individuals with an expanded number of CAG repeats have progressive worsening of their saccadic eye movements, olfactory identification and neurocognitive performance as they approach clinically-recognized, disease onset. If we are successful, we will have identified biomarkers that are ideally suited for studies of neuroprotective agents and which could be used in future treatments to delay or eliminate the onset of the symptoms of HD. [unreadable] [unreadable] [unreadable]